Collagen imaging: Bridging the gap between microscopy and the clinic

It’s expected that almost 250,000 women in the United States will be diagnosed with invasive breast cancer in 2016 alone.

Michael Pinkert
Michael Pinkert

When it comes to diagnosing breast cancer and predicting how the disease will progress in a patient, current practice is seeing a gap between the imaging information scientists can get from a high resolution microscope and the lower resolution images typically gathered in the clinical setting.

Michael Pinkert, a graduate researcher in the Morgridge Institute Medical Engineering group and doctoral student in medical physics at UW-Madison, is trying to bridge that imaging gap.

“The goal is to always progress medical science so we can improve patient care, improve patient diagnosis, improve patient treatment,” says Pinkert. “We currently have methods of patient care that are imperfect, and new technologies can serve as great improvements.”

Pinkert is developing a hardware, procedure, and software framework for comparing images from two common clinical imaging methods, magnetic resonance imaging (MRI) and ultrasound, with second harmonic generation (SHG) microscopy.

Optical microscopy such as SHG has a much higher resolution than clinical imaging methods like MRI or ultrasound—it’s the difference between taking a picture of individual cells or fibers versus an entire breast tissue region. The challenge is correlating the characteristics seen at the microscopic, submicron level to what doctors see in patients in the clinic setting.

This challenge of multiscale is a major theme of the Morgridge Engineering group and this multiscale collagen research is one of the driving project of the Multiscale initiative.

Both a cancerous tumor and its microenvironment, the area surrounding the tumor, play a critical role in how the cancer develops, Pinkert says.

In particular, the way collagen fibers are aligned around a tumor boundary gives insight into how breast cancer is going to progress. A tumor can also rearrange collagen into different alignments. Having perpendicularly-aligned fibers, for example, is thought to be providing the tumor with highways that can be used to send cancer cells to other parts of the body.

Knowing collagen alignment can both forecast disease outcomes and signal how a cancer is spreading itself motivated Pinkert to use SHG microscopy—it’s the primary technology for imaging collagen.

Combining this type of microscopy with MRI and ultrasound, two of the most common ways clinicians image a patient’s breast tissue, will make the integrated process easier to implement in the clinical setting.

“We want to develop these techniques in a clinically-relevant manner,” Pinkert says. “We’re including the three modalities we’ve chosen for a couple reasons: they’re non-ionizing and patient safe, and clinicians are already familiar with MRI and ultrasound technology.”

Pinkert is working in collaboration with Kevin Eliceiri, investigator in Morgridge Medical Engineering and director of the Laboratory for Optical and Computational Instrumentation (LOCI), and UW-Madison professors Tim Hall, Medical Physics; Paul Campagnola, Biomedical Engineering,; Jeremy Rogers, Biomedical Engineering; Patti Keely, Cell and Regenerative Biology; Lonie Salkowski, Radiology; and Walter Block, Biomedical Engineering.

As of now the team is primarily interested in finding out which properties can be measured, the best methods for doing so, and how these procedures could be best implemented in the clinical setting.